Differences in Transport Mechanisms of trans-1-Amino-3-[18F]Fluorocyclobutanecarboxylic Acid in Inflammation,Prostate Cancer,and Glioma Cells: Comparison with l-[Methyl-11C]Methionine and 2-Deoxy-2-[18F]Fluoro-d-Glucose

Purpose

We aimed to elucidate trans-1-amino-3-[¹⁸F]fluorocyclobutanecarboxylic acid (anti-[¹⁸F]FACBC) uptake mechanisms in inflammatory and tumor cells, in comparison with those of l-[methyl-¹¹C]methionine ([¹¹C]Met) and 2-deoxy-2-[¹⁸F]fluoro-d-glucose ([¹⁸F]FDG).

Procedures

Using carbon-14-labeled tracers, in vitro time-course, pH dependence, and competitive inhibition uptake experiments were performed in rat inflammatory (T cells, B cells, granulocytes, macrophages), prostate cancer (MLLB2), and glioma (C6) cells.

Results

Anti-[¹⁴C]FACBC uptake ratios of T/B cells to tumor cells were comparable, while those of granulocytes/macrophages to tumor cells were lower than those for [¹⁴C]FDG. Over half of anti-[¹⁴C]FACBC uptake by T/B and tumor cells was mediated by Na⁺-dependent amino acid transporters (system ASC), whereas most [¹⁴C]Met transport in all cells was mediated by Na⁺-independent carriers (system L).

Conclusions

The low anti-[¹⁸F]FACBC accumulation in granulocytes/macrophages may be advantageous in discriminating inflamed regions from tumors. The significant anti-[¹⁸F]FACBC uptake in T/B cells may cause false-positives in some cancer patients who undergo FACBC-positron emission tomography (PET).     

Pilot Evaluation of Anti-1-amino-2-[18F] fluorocyclopentane-1-carboxylic acid (anti-2-[18F] FACPC) PET-CT in Recurrent Prostate Carcinoma

Molecular Imaging and Biology - Anti-1-amino-2-[18F]fluorocyclopentane-1-carboxylic acid (anti-2-[18F]FACPC) is an unnatural alicyclic amino acid radiotracer with high uptake in the DU-145 prostate...     

Initial Experience with the Radiotracer Anti-1-amino-3-[18F]Fluorocyclobutane-1-Carboxylic Acid (Anti-[18F]FACBC) with PET in Renal Carcinoma

Purpose

Assessment of renal masses with conventional imaging may be challenging. Anti-1-amino-3-[¹⁸F]fluorocyclobutane-1-carboxylic acid (anti-[18F]FACBC) is a synthetic l-leucine analog with relatively little renal excretion. The present study examines anti-[¹⁸F]FACBC positron emission tomography uptake in patients with renal masses.

Procedures

Six patients with seven renal lesions were imaged dynamically for 2 h after injection of 10–10.9 mCi (370–403 MBq) anti-[¹⁸F]FACBC. Lesions were evaluated qualitatively and quantitatively and correlated with histology.

Results

Four clear cell and one Rosai–Dorfman lesion were hypo/isointense to normal cortex; two papillary lesions in the same patient were hyperintense. Mean SUV_max?±?SD at 30 min was 2.8?±?0.24 for clear cell carcinomas and 4.5?±?1.7 for papillary cell lesions. Mean SUV_max/SUV_mean ratios?±?SD of lesion to normal cortex at 30 min was 1.15?±?0.19 for the clear cell carcinomas and 2.3?±?0.84 for papillary cell.

Conclusions

In this small patient sample, relative amino acid transport compared with renal cortex is elevated in renal papillary cell carcinoma but not in clear cell carcinoma.     

Pilot Study of the Utility of the Synthetic PET Amino-Acid Radiotracer Anti-1-Amino-3-[18F]Fluorocyclobutane-1-Carboxylic Acid for the Noninvasive Imaging of Pulmonary Lesions

Purpose

Anti-1-amino-3-[¹⁸F]fluorocyclobutane-1-carboxylic acid (anti-3-[¹⁸F]FACBC) is a synthetic amino acid positron emission tomography (PET) radiotracer with utility in detection of prostate carcinoma and brain tumors and has also been shown to have uptake in lung tumor cell lines. The purpose of this study is to determine the uptake characteristics of anti-3-[¹⁸F]FACBC in lung carcinoma and if this radiotracer may help characterize pulmonary lesions.

Procedures

Ten patients with pulmonary lesions scheduled for surgical resection or biopsy underwent 45-min dynamic PET-CT imaging of the thorax after IV injection of 214.6–384.8MBq of anti-3-[¹⁸F]FACBC. Anti-3-[¹⁸F]FACBC uptake was compared with that of routine 2-deoxy-2-[¹⁸F]fluoro-d-glucose ([¹⁸F]FDG) PET-CT scans of the same patient and validated with a combination of pathology, imaging and clinical follow-up. Immunohistochemistry for Ki-67 was performed on tissue samples.

Results

There were nine malignant (seven lung nodules and two mediastinal nodes), two inflammatory, and one carcinoid lesion ranging from 1 to 3.75 cm. Mean(±SD) SUV_max of malignant lesions was 6.2(±2.6), 5.9(±2.7), 5.9(±3.4), and 5.7(±3.3), at 8, 16, 28, and 40 min, respectively; while for inflammatory lesions at the same time points, 4.1(±0.6), 3.3(±0.9), 2.2(±0.03), and 2.3(±0.03), respectively. The carcinoid tumor had SUV_max of 2.8, 2.6, 1.5, and 0.9 at similar time points. Mean SUV_max of all malignant lesions was higher than that of inflammatory lesions for anti-3-[¹⁸F]FACBC, and was statistically significant at greater than 28 min post-radiotracer infusion (p?<?0.05). There was no significant correlation of anti-3-[¹⁸F]FACBC activity with Ki67, though there was a positive trend. There was a strong correlation between anti-3-[¹⁸F]FACBC and [¹⁸F]FDG uptake.

Conclusions

Anti-3-[¹⁸F]FACBC uptake in malignant lesions is greater than in inflammatory lesions with a higher degree of separation of uptake on delayed imaging. More comprehensive study is required to determine the diagnostic performance of anti-3-[¹⁸F]FACBC in the characterization of pulmonary lesions.     

[18F]-JK-PSMA-7 PET/CT Under Androgen Deprivation Therapy in Advanced Prostate Cancer

Purpose

PSMA imaging is frequently used for monitoring of androgen deprivation therapy (ADT) in prostate cancer. In a previous study, [¹⁸F]-JK-PSMA-7 exhibited favorable properties for tumor localization after biochemical recurrence. In this retrospective study, we evaluated the performance of [¹⁸F]-JK-PSMA-7 under ADT.

Procedures

We examined the performance of [¹⁸F]-JK-PSMA-7 in 70 patients (first cohort) with increasing or detectable PSA values under ADT (PSA < 2 ng/ml for 21/70 patients). We further analyzed 58 independent patients with PSA levels < 2 ng/ml under ADT, who were imaged with [⁶⁸Ga]PSMA-11 or [¹⁸F]DCFPyL (second cohort). Finally, we compared detection rates between [¹⁸F]-JK-PSMA-7, [⁶⁸Ga]PSMA-11, and [¹⁸F]DCFPyL.

Results

In the first cohort, we detected [¹⁸F]-JK-PSMA-7-positive lesions in 63/70 patients. In patients with PSA levels ≥ 2 ng/ml, the detection rate was 100 % (49/49). In patients with PSA < 2 ng/ml, the detection rate was significantly lower (66.7 %, 14/21, p = 9.7 × 10^?5) and dropped from 85.7 % (12/14, PSA levels between 0.3 and 2.0 ng/ml) to 28.6 % (2/7) for PSA levels < 0.3 ng/ml (p = 1.73 × 10^?2). In the second cohort (PSA < 2 ng/ml), the detection rate was 79.3 % (46/58) for [⁶⁸Ga]PSMA-11 or [¹⁸F]DCFPyL. Again, the detection rate was significantly higher (p = 1.1 × 10^?2) for patients with PSA levels between 0.3 and 2.0 ng/ml (87.0 %, 40/46) relative to those with PSA levels < 0.3 ng/ml (50 %, 6/12). No significant difference was found between [¹⁸F]-JK-PSMA-7 and [⁶⁸Ga]PSMA-11 or [¹⁸F]DCFPyL in patients with PSA levels < 2 ng/ml (p = 0.4295).

Conclusion

[¹⁸F]-JK-PSMA-7 PET showed a high detection rate in patients with PSA levels ≥ 0.3 ng/ml under ADT. The lower PSA threshold of 0.3 ng/ml for high detection rates was consistent across the three PSMA ligands. Thus, PSMA imaging is suitable for clinical follow-up of patients with increasing PSA levels under ADT.

     

Simultaneous PET/MRI in the Evaluation of Breast and Prostate Cancer Using Combined Na[18F]F and [18F]FDG: a Focus on Skeletal Lesions

Molecular Imaging and Biology - The purpose of this study is to prospectively evaluate the performance of sodium 18F]fluoride (Na[18F]F)/2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) simultaneous...     

Response to: Letter to the Editors: Re: Simultaneous PET/MRI in the Evaluation of Breast and Prostate Cancer Using Combined Na[18F]F and [18F]FDG: A Focus on Skeletal Lesions

Molecular Imaging and Biology -     

The Effect of Chirality on the Application of 5-[18F]Fluoro-Aminosuberic Acid ([18F]FASu) for Oxidative Stress Imaging

Molecular Imaging and Biology - The cystine transporter, system xC-, plays a crucial role in sustaining redox homeostasis and is reported to be overexpressed in several cancer subtypes....     

How Long of a Dynamic 3′-Deoxy-3′-[18F]fluorothymidine ([18F]FLT) PET Acquisition Is Needed for Robust Kinetic Analysis in Breast Cancer?

Molecular Imaging and Biology - To quantitatively evaluate the minimally required scanning time of 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT) positron emission tomography (PET) dynamic...     

Glucose-6-phosphatase Expression–Mediated [18F]FDG Efflux in Murine Inflammation and Cancer Models

Molecular Imaging and Biology - 2-Deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) accumulation in inflammatory lesions can confound the diagnosis of cancer. In this study, we investigated [18F]FDG...     

Adenine Nucleotide Translocase 2 as an Enzyme Related to [18F] FDG Accumulation in Various Cancers

Molecular Imaging and Biology - Although glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) are known as major proteins involved in the molecular mechanisms for accumulating...     

Preclinical Evaluation of 4-[<Superscript>18</Superscript>F]Fluoroglutamine PET to Assess ASCT2 Expression in Lung Cancer

Purpose

Alanine-serine-cysteine transporter 2 (ASCT2) expression has been demonstrated as a promising lung cancer biomarker. (2S,4R)-4-[¹⁸F]Fluoroglutamine (4-[¹⁸F]fluoro-Gln) positron emission tomography (PET) was evaluated in preclinical models of non-small cell lung cancer as a quantitative, non-invasive measure of ASCT2 expression.

Procedures

In vivo microPET studies of 4-[¹⁸F]fluoro-Gln uptake were undertaken in human cell line xenograft tumor-bearing mice of varying ASCT2 levels, followed by a genetically engineered mouse model of epidermal growth factor receptor (EGFR)-mutant lung cancer. The relationship between a tracer accumulation and ASCT2 levels in tumors was evaluated by IHC and immunoblotting.

Result

4-[¹⁸F]Fluoro-Gln uptake, but not 2-deoxy-2-[¹⁸F]fluoro-D-glucose, correlated with relative ASCT2 levels in xenograft tumors. In genetically engineered mice, 4-[¹⁸F]fluoro-Gln accumulation was significantly elevated in lung tumors, relative to normal lung and cardiac tissues.

Conclusions

4-[¹⁸F]Fluoro-Gln PET appears to provide a non-invasive measure of ASCT2 expression. Given the potential of ASCT2 as a lung cancer biomarker, this and other tracers reflecting ASCT2 levels could emerge as precision imaging diagnostics in this setting.

     

Comparison of Hypermetabolic and Hypoxic Volumes Delineated on [18F]FDG and [18F]Fluoromisonidazole PET/CT in Non-small-cell Lung Cancer Patients

Purpose

The high rates of failure in the radiotherapy target volume suggest that patients with stage II or III non-small-cell lung cancer (NSCLC) should receive an increased total dose of radiotherapy. 2-Deoxy-2-[¹⁸F]fluoro-d-glucose ([¹⁸F]FDG) and [¹⁸F]fluoromisonidazole ([¹⁸F]FMISO) (hypoxia) uptake on pre-radiotherapy positron emission tomography (PET)/X-ray computed tomography (CT) have been independently reported to identify intratumor subvolumes at higher risk of relapse after radiotherapy. We have compared the [¹⁸F]FDG and [¹⁸F]FMISO volumes defined by PET/CT in NSCLC patients included in a prospective study.

Procedures

Thirty-four patients with non-resectable lung cancer underwent [¹⁸F]FDG and [¹⁸F]FMISO PET/CT before (pre-RT) and during radiotherapy (around 42 Gy, per-RT). The criteria were to delineate 40 % and 90 % SUVmax thresholds on [¹⁸F]FDG PET/CT (metabolic volumes), and SUV >?1.4 on pre-RT [¹⁸F]FMISO PET/CT (hypoxic volume). The functional volumes were delineated within the tumor volume as defined on co-registered CTs.

Results

The mean pre-RT and per-RT [¹⁸F]FDG volumes were not statistically different (30.4 cc vs 22.2; P?=?0.12). The mean pre-RT SUVmax [¹⁸F]FDG was higher than per-RT SUVmax (12.7 vs 6.5; P?<?0.0001). The mean [¹⁸F]FMISO SUVmax and volumes were 2.7 and 1.37 cc, respectively. Volume-based analysis showed good overlap between [¹⁸F]FDG and [¹⁸F]FMISO for all methods of segmentation but a poor correlation for Jaccard or Dice Indices (DI). The DI maximum was 0.45 for a threshold at 40 or 50 %.

Conclusion

The correlation between [¹⁸F]FDG and [¹⁸F]FMISO uptake is low in NSCLC, making it possible to envisage different management strategies as the studies in progress show.

     

Tantalum [18O]water target for the production of [18F]fluoride with high reactivity for the preparation of 2-deoxy-2-[18F]fluoro-D-glucose.

PURPOSE: To develop a new tantalum [18O]water target for the routine production of reactive, no-carrier-added [18F]fluoride ion in Curie amounts for the synthesis of radiopharmaceuticals. PROCEDURES: The tantalum target body was filled with 0.86 mL of 95% enriched [18O]water and irradiated with 10.2 MeV protons on target with beam currents of 26-40 microA for 60-90 min. [18F]Fluoride ion produced is trapped in an anion exchange resin cartridge and the expensive [18O]water is recovered for recycling. The [18F]fluoride ion is released from the resin by elution with a dilute solution of K(2)CO(3) and utilized in the synthesis of 2-deoxy-2-[18F]fluoro-D-glucose (FDG). RESULTS: Using the tantalum target, Curie levels of no-carrier-added [18F]fluoride ion (specific activity: >30,000 Ci/mmol) were reliably and reproducibly produced (n > 100), from which FDG was synthesized in 70% radiochemical yield. CONCLUSION: Tantalum [18O]water target body for the production of [18F]fluoride ion has the best characteristics from the standpoint of [18F]fluoride ion recovery and its radiochemical reactivity and low induced activation. This new target has the potential to replace the currently used silver and titanium [18O]targets for the routine production of [18F]fluoride ion.     

Synthesis and evaluation of 3′-[18F]fluorothymidine-5′-squaryl as a bioisostere of 3′-[18F]fluorothymidine-5′-monophosphate

The squaryl moiety has emerged as an important phosphate bioisostere with reportedly greater cell permeability. It has been used in the synthesis of several therapeutic drug molecules including nucleoside and nucleotide analogues but is yet to be evaluated in the context of positron emission tomography (PET) imaging. We have designed, synthesised and evaluated 3′-[¹⁸F]fluorothymidine-5′-squaryl ([¹⁸F]SqFLT) as a bioisostere to 3′-[¹⁸F]fluorothymidine-5′-monophosphate ([¹⁸F]FLTMP) for imaging thymidylate kinase (TMPK) activity. The overall radiochemical yield (RCY) was 6.7 ± 2.5% and radiochemical purity (RCP) was >90%. Biological evaluation in vitro showed low tracer uptake (<0.3% ID mg⁻¹) but significantly discriminated between wildtype HCT116 and CRISPR/Cas9 generated TMPK knockdown HCT116^shTMPK−. Evaluation of [¹⁸F]SqFLT in HCT116 and HCT116^shTMPK− xenograft mouse models showed statistically significant differences in tumour uptake, but lacked an effective tissue retention mechanism, making the radiotracer in its current form unsuitable for PET imaging of proliferation.

[¹⁸F]SqFLT was developed to bypass thymidine kinase 1 (TK1) and evaluated for PET imaging of DNA synthesis.     

A Pilot Trial Evaluating Zoledronic Acid Induced Changes in [<Superscript>18</Superscript>F]FMAU-Positron Emission Tomography Imaging of Bone Metastases in Prostate Cancer

Purpose

We conducted a pilot trial utilizing [¹⁸F]FMAU [1-(2′-deoxy-2′-[¹⁸F]fluoro-β-d-arabinofuranosyl thymine] as a tumor tracer in positron emission tomography (PET) and evaluated its reproducibility, and changes in maximum and peak standardized uptake value (SUVmax and SUVpeak) with zoledronic acid treatment in castrate resistant prostate cancer (CRPC) patients with bone metastases (BM).

Procedures

Eligible patients had CRPC with radiographic evidence of BM and creatinine clearance >30 ml/min. Two baseline [¹⁸F]FMAU-PET scans (about 1 week apart, range 2–12 days) were obtained for testing reproducibility. Zoledronic acid 4 mg was infused over 15 min within 1 week after second scan and a third PET scan was obtained 7 days later. The bony lesion with the highest uptake on the first scan was compared with later scans. Bone turnover markers and prostate-specific antigen (PSA) were obtained pre- and post-therapy. PET response was defined as decline in SUVmean of ≥15 % after zoledronic acid.

Results

Eleven patients were evaluated, median age was 65 years, five were African-American and six were Caucasian, and median PSA level was 36.3 ng/ml (range 1.0–1209.3). Notably, the range of absolute percent SUVmax changes varied between 0.77 and 54.7, and only nine measurements were greater than one (1.09–2.19). Zoledronic acid did not appreciably change FMAU uptake. No clinical response was noted. Urine N-telopeptide (NTx) was markedly decreased in all patients after zoledronic acid and serum bone-specific alkaline phosphatase (BSAP) registered a modest change. Urine NTx correlated more closely with SUV max than serum BSAP.

Conclusions

FMAU tracer was able to detect bone metastases in CRPC patients but uptake was highly variable in bony lesions. Zoledronic acid did not produce an appreciable change in scans. Future investigations of FMAU tracer as a marker of early response in CRPC is recommended.

     

脂肪酸合成酶表达与前列腺癌发生发展和转移的关系

[目的]探讨脂肪酸合成酶(fatty acid synthase,FASE)的表达与前列腺癌(Pca)发生发展和转移的关系.[方法]采用免疲组化SP法检测58例Pca、29例前列腺上皮内瘤(PIN)、20例良性前列腺增生(BPH)组织中FASE的表达,比较其表达与Pca临床病理特征的关系.[结果]良性前列腺增生、前列腺上皮内瘤和Pca组织中FASE阳性表达率呈增高趋势,差异有统计学意义(P<0.05).FASE表达与Pca组织分化程度、Gleason分级和临床病理分期有关(P<0.05),与Pca淋巴结转移无关(P>0.05).[结论]FASE异常表达增高在Pca的恶性进展中起重要作用,检测FASE的表达有帮助于判断其病期及预后.     

Brown Adipose Tissue in Breast Cancer Evaluated by [18F] FDG-PET/CT

Molecular Imaging and Biology - Recently brown adipose tissue (BAT) activation has been proposed to have a possible role in breast cancer. The aim of this study was to evaluate BAT activation in...     

Correction to: [18F]-FDG-PET/CT and [18F]-FAZA-PET/CT Hypoxia Imaging of Metastatic Thyroid Cancer: Association with Short-Term Progression after Radioiodine Therapy

Molecular Imaging and Biology - This article was update to correct the spelling of Takashi Yoshiura’s name; it is correct as displayed here.